Paper

Bidirectional Communication between the Brain and the Immune System: Implications for Physiological Sleep and Disorders with Disrupted Sleep
Dianne Lorton^{a, b}, Cheri L. Lubahn^a, Chris Estus^a, Brooke A. Millar^c, Jeffery L. Carter^c, Carlo A. Wood^c, Denise L. Bellinger<sup>c

a</sup>Hoover Arthritis Research Center, Sun Health Research Institute, Sun City, Ariz.,
^bLife Science Department, Arizona State University, Tempe, Ariz., and
^cDepartment of Human Anatomy and Pathology, Loma Linda University School of Medicine, Loma Linda, Calif., USA

Address of Corresponding Author

Neuroimmunomodulation 2006;13:357-374 (DOI: 10.1159/000104864)

  Key Words

• Cytokines
• Nervous system
• Immune system
• Signaling
• Rheumatoid arthritis
• Sleep deprivation
• Sickness behavior
• Hypothalamic-pituitary-adrenal axis
• Sympathetic nervous system

  Abstract

This review describes mechanisms of immune-to-brain and brain-to-immune signaling involved in mediating physiological sleep and altered sleep with disease. The central nervous system (CNS) modulates immune function by signaling target cells of the immune system through autonomic and neuroendocrine pathways. Neurotransmitters and hormones produced and released by these pathways interact with immune cells to alter immune functions, including cytokine production. Cytokines produced by cells of the immune and nervous systems regulate sleep. Cytokines released by immune cells, particularly interleukin-1 and tumor necrosis factor-, signal neuroendocrine, autonomic, limbic and cortical areas of the CNS to affect neural activity and modify behaviors (including sleep), hormone release and autonomic function. In this manner, immune cells function as a sense organ, informing the CNS of peripheral events related to infection and injury. Equally important, homeostatic mechanisms, involving all levels of the neuroaxis, are needed, not only to turn off the immune response after a pathogen is cleared or tissue repair is completed, but also to restore and regulate natural diurnal fluctuations in cytokine production and sleep. The immune system's ability to affect behavior has important implications for understanding normal and pathological sleep. Sleep disorders are commonly associated with chronic inflammatory diseases and chronic age- or stress-related disorders. The best studied are rheumatoid arthritis, fibromyalgia and chronic fatigue syndromes. This article reviews our current understanding of neuroimmune interactions in normal sleep and sleep deprivation, and the influence of these interactions on selected disorders characterized by pathological sleep.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Dianne Lorton, PhD
Hoover Arthritis Center
10515 West Santa Fe Drive
Sun City, AZ 85372 (USA)
Tel. +1 623 87 5454, Fax +1 623 876 5461, E-Mail dianne.lorton@sunhealth.org

  Article Information

Published online: August 6, 2007
Number of Print Pages : 18
Number of Figures : 4, Number of Tables : 0, Number of References : 189